Thromboembolic prevention in athletes: management of anticoagulation in sports players affected by atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia that poses a significant risk of stroke and thromboembolic events. Anticoagulation therapy is essential for preventing stroke in patients with AF. An increasing number of people of all ages, including cardiac patients, approach physical activity as both a leisure-time exercise and a competitive sport. Therefore, patients at risk of AF are increasingly allowed to practice sports activities. Management of oral anticoagulant therapy (OAT) in these patients is extremely challenging because of the need to balance the risks and benefits of medications, considering both hemorrhagic (in case of trauma) and ischemic complications when the drugs are avoided. Official recommendations are limited for these patients and forbid sports that increase the risk of trauma and consequent bleeding in most cases. These recommendations are strongly influenced by the "traditional" management of OAT, which mainly involves coumarin derivatives. Non-vitamin K antagonist direct oral anticoagulants (DOACs), with their more favorable pharmacokinetic-pharmacodynamic profile than that of coumarin derivatives, may represent an opportunity to modify the approach to sports activity in patients with AF and indications for OAT. This study aimed to review the use of anticoagulants in athletes with AF, highlight their efficacy and safety, and provide practical considerations regarding their management.

Free Vibrations of Bernoulli-Euler Nanobeams with Point Mass Interacting with Heavy Fluid Using Nonlocal Elasticity.

Eigenfrequencies of a nanobeam with a point mass interacting with a heavy fluid are calculated using Bernoulli-Euler kinematics and consistent nonlocal elasticity model. The proposed approach is applicable to a variety of nanotechnology materials and structures, especially mass nanosensors. Eigenfrequencies are compared with those of local theory and conclusions are drawn. Influence of nonlocal effects, heavy fluid interaction and added point mass on dynamic responses is analyzed and the results are documented. Size phenomena are noted and discussed.

Dynamics of Stress-Driven Two-Phase Elastic Beams.

The dynamic behaviour of micro- and nano-beams is investigated by the nonlocal continuum mechanics, a computationally convenient approach with respect to atomistic strategies. Specifically, size effects are modelled by expressing elastic curvatures in terms of the integral mixture of stress-driven local and nonlocal phases, which leads to well-posed structural problems. Relevant nonlocal equations of the motion of slender beams are formulated and integrated by an analytical approach. The presented strategy is applied to simple case-problems of nanotechnological interest. Validation of the proposed nonlocal methodology is provided by comparing natural frequencies with the ones obtained by the classical strain gradient model of elasticity. The obtained outcomes can be useful for the design and optimisation of micro- and nano-electro-mechanical systems (M/NEMS).

Elastostatics of Bernoulli-Euler Beams Resting on Displacement-Driven Nonlocal Foundation.

The simplest elasticity model of the foundation underlying a slender beam under flexure was conceived by Winkler, requiring local proportionality between soil reactions and beam deflection. Such an approach leads to well-posed elastostatic and elastodynamic problems, but as highlighted by Wieghardt, it provides elastic responses that are not technically significant for a wide variety of engineering applications. Thus, Winkler's model was replaced by Wieghardt himself by assuming that the beam deflection is the convolution integral between soil reaction field and an averaging kernel. Due to conflict between constitutive and kinematic compatibility requirements, the corresponding elastic problem of an inflected beam resting on a Wieghardt foundation is ill-posed. Modifications of the original Wieghardt model were proposed by introducing fictitious boundary concentrated forces of constitutive type, which are physically questionable, being significantly influenced on prescribed kinematic boundary conditions. Inherent difficulties and issues are overcome in the present research using a displacement-driven nonlocal integral strategy obtained by swapping the input and output fields involved in Wieghardt's original formulation. That is, nonlocal soil reaction fields are the output of integral convolutions of beam deflection fields with an averaging kernel. Equipping the displacement-driven nonlocal integral law with the bi-exponential averaging kernel, an equivalent nonlocal differential problem, supplemented with non-standard constitutive boundary conditions involving nonlocal soil reactions, is established. As a key implication, the integrodifferential equations governing the elastostatic problem of an inflected elastic slender beam resting on a displacement-driven nonlocal integral foundation are replaced with much simpler differential equations supplemented with kinematic, static, and new constitutive boundary conditions. The proposed nonlocal approach is illustrated by examining and analytically solving exemplar problems of structural engineering. Benchmark solutions for numerical analyses are also detected.

Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I) expression in prostatic cancer.

Despite evidence implicating the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, its precise role remains unclear. In this study we investigated the differential expression of IGF-I, IGF-II and their type I receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues. Using immunohistochemistry and in situ hybridization techniques, we analyzed 43 paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. We then determined a possible correlation of the immunohistochemical and in situ findings with two known prognostic clinical-pathological indices: Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43 frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and IGFR-I protein and mRNA; all levels increased significantly from normal tissue to PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher in epithelium than in stroma, whereas expression of IGF ligands differed. In normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in epithelium. Conversely, in Pca tissue, both factors were more strongly expressed in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR-I levels highest in the epithelium. IGF-II protein and mRNA reached their highest levels in prostate tumors with high Gleason scores. These findings indicate that the IGF system changes as prostate tissue progresses from a normal to a malignant state. Differential expression of certain IGF system components in Pca may be associated with the malignant phenotype and more aggressive tumor behavior. Hence IGFs could serve to predict the outcome of prostatic cancer.

Mutational analysis of StAR gene in adrenal tumors.

Adrenal adenomas and carcinomas are mostly monoclonal, suggesting that a genetic alteration in a progenitor cell may contribute to their development. However, the molecular pathogenesis of these tumors still remains unclear. It has been already excluded that activating mutations of the ACTH receptor or of G protein stimulator alpha sub-units, affecting cAMP pathway, is involved in the tumorigenesis. Therefore, this work has been focused on post-transductional (ACTH) signal alterations and in particular on the mutational analysis of the Steroid Acute Regulatory protein (StAR) gene to verify whether somatic mutations or genomic polymorphisms of this gene may be correlated with adrenal tumorigenesis. Tissue DNA was extracted from 40 functional and non-functional adrenocortical tumors that were removed from patients aged between 17 and 72 years (mean 43 +/- 4). Blood DNA was obtained from 24 patients (aged between 26 and 70 years) affected by adrenal tumors and from 100 healthy subjects without radiological and clinical evidence of adrenal masses, aged between 25-35 years (90 Caucasians and 10 Africans). The DNA was used as the template for the amplification of the StAR gene using the polymerase chain reaction. The amplified DNA of each exon of the StAR gene was purified and sequenced in automatic sequenciator. With the exception of exon 5 showing in codon 203 an homozygous missense mutation, the sequence of the other exons of the StAR gene resulted normal in all tumors studied. The same homozygous mutation (Asp203Ala) was observed in the sequence of exon 5 performed on genomic DNA of the 24 affected patients and in the control subjects. The homozygosity of the mutation observed in all patients (either in tissue or blood samples) and in control subjects, independently of their ethnic origin, led us to suggest that the Asp203Ala cannot be considered as mutation or as polymorphism, but that it must be considered as a mistake in the sequence entered in the Genbank, which needs to be modified accordingly. These data, and those up to now reported in the literature, allow us to suggest that mutations of the gene coding for the protein involved in the initial step of the steroidogenesis could not be considered as a possible cause for the development of adrenal tumors.